Selective Serotonin Reuptake Inhibitors Selective serotonin reuptake inhibitors (SSRIs) have gained notoriety as a common cause of several manifestations of sexual dysfunction. SSRI-induced ED rather than sexual dysfunction, though, is rarely reported in the literature and is limited mostly to case reports.

Antihypertensive Agents Several antihypertensive agents have been implicated in ED, yet the evidence is limited. Older thiazide diuretic treatments have been associated with mild effects on erectile function.

Many of these studies have limited clinical implications as they were conducted with chlorthalidone, a thiazide-like diuretic. A recent study suggested that beta-blocker-induced ED is likely psychogenic rather than organic. Clonidine is reported to cause ED in both human and animal studies through agonism of central alpha-2 adrenoreceptors.

Statins Statins are HMG-CoA reductase inhibitors that are a commonly used medication for the treatment of hyperlipidemia. Do et al. conducted a study to investigate the association between exposure to statins and the occurrence of ED. The study was limited to males age 18–30. They found a statistically significant association for statins with induction and worsening of ED. Further studies are needed to distinguish the severity of the effect on ED between the many different statin drugs that are currently in use.

In cases of ED and hypogonadism, recent randomized controlled trials suggest that patients who are initially refractory to type V phosphodiesterase (PDE5) inhibitors (sildenafil, vardenafil, and tadalafil) can be rescued by the concurrent administration of testosterone with PDE5 inhibitors. The administration of testosterone alone, without PDE5 inhibitors, has also been shown to improve erectile function in hypogonadal men. Androgen deficiency has been shown to result in penile tissue atrophy, increased adipose tissue within the subtunical region, and severe venous leak resulting in ED. All of these effects can potentially be reversed by the administration of testosterone. A number of distinct pathways of the endocrine system lead to ED when functioning abnormally. Several studies show that hypogonadism of any cause is an uncommon cause of ED.

The role of testosterone and other androgens in the achievement and maintenance of penile erection is controversial due to the lack of standardization in defining low testosterone. A recent study found that the prevalence of “low testosterone” in men with ED was largely dependent on the accepted definition of this disease state. Reported prevalence increased from 7% to 47% for definitions of testosterone level less than 200 ng/dL versus less than 400 ng/dL, respectively.

The role of androgens in erectile physiology as demonstrated in the animal model is to potentiate the effects of neurologic and vascular/ endothelial mechanisms of erection. Although tumescence is possible with decreased testosterone, the quality of the erection may be diminished. Importantly, the efficacy of PDE5 inhibitors is greatly diminished in the absence of androgens. Furthermore, in rats, dihydrotestosterone is the primary androgen responsible for erectile physiology at the level of the endothelial cell. Mexican Viagra Online

This decline in serum testosterone level can be age-related or the result of hypogonadism of any cause. A recently published study evaluated the prevalence of both hypogonadism and depression in men presenting to an ED clinic. They also tested the correlation of hypogonadism and the presence of depressive symptoms. They indeed found hypogonadal men to be more likely to have overt depression scores compared to eugonadal controls. The authors derived the conclusion that depression symptoms are strongly associated with hypogonadism and that physicians should consider the evaluation of testosterone levels in men with overt symptoms of depression.

KQ 1. The clinical utility of routine blood tests—testosterone, prolactin, LH, FSH – in identifying and affecting therapeutic outcomes for treatable causes of ED was examined using reports of measurements of serum testosterone, FSH, LH, prolactin, and/or other hormone levels, (but not gonadotrophin-releasing hormone [GnRH], Inhibin, Activin, or Follistim). It was also examined in reports of the prevalence of reversible hormonal disorders in males with erectile dysfunction. The study selection criteria included the following:

EthanolThe role of ethanol, while classically thought to impede erectile function, has been less clear in the literature. Despite the association of alcohol consumption and sexual activity, very little objective evidence exists on the effect of acute ethanol intoxication on erectile function. The data on chronic ethanol exposure is also mixed. Ethanol exposure in an animal model showed histologic evidence of both endothelial damage and metabolicdysfunction.

Impairment of smooth muscle relaxation due to endothelial dysfunction was pronounced while neurogenic smooth muscle relaxation remained intact. Age and Chronic Illness There is no consensus as to whether ED is a nonpathologic, natural aspect of aging in healthy males, though older males do have higher rates of ED. The association between naturally declining testosterone level in older males, socalled andropause, and ED, is complex, but no clear association is found to date.

Interestingly, penile vibrotactile sensation of the penis decreases significantly with age, but this has not been directly linked with ED.

Approximately 82% of men with chronic renal failure (CRF) on hemodialysis have some degree of erectile function, with 45% having severe ED. Additionally, regardless of treatment, patient with CRF have significantly decreased mean nocturnal penile tumescence when compared to both normal and chronically ill controls. The pathophysiology of ED in patients with CRF is complex. A majority of men with CRF have hyperprolactinemia. Uremia also interferes with the HPA such that oligospermia, azoospermia, and impaired steriodogenesis with elevations in LH are common in uremic men.

Zinc deficiency has also been postulated as a potential cause of ED in uremic men and has been targeted for possible therapeutic interventions.

KQ 3a. The incidence of specific harms such as Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) and penile fibrosis associated with use of PDE–5 inhibitor and injection therapies, respectively. The review included reports of non-RCTs or observational studies. For identification of data on fibrosis related to use of injection therapies, only studies with at least 6 months of followup were included.

Outcomes: NAION, penile fibrosis Systematic and narrative reviews, case reports, editorials, commentaries or letters to the editor were excluded for all questions except Q3–a (specific harms). Studies evaluating interventions such as penile implant devices or natural health products used for the treatment of ED were also excluded.

The results of the literature search were uploaded to the software program TrialStat SRS version 4.0 along with screening questions developed by the review team and any supplemental instructions. A calibration exercise was undertaken to pilot and refine the screening process. One reviewer screened bibliographic records (i.e., title, authors, key words, abstract) using broad screening criteria (Appendix B). All potentially relevant records and those records that did not contain enough information to determine eligibility (e.g. no abstract was available) were retained. The reasons for exclusion are noted in the QUOROM flow diagram. Two reviewers independently performed full-text relevance screening. Disagreements were resolved by consensus.

Relevant studies were then evaluated to determine study design and were categorized accordingly for inclusion by question. The level of eligible evidence on efficacy was limited to RCTs, since systematic bias is minimized in RCTs compared with all other study designs (e.g. cross-sectional, retrospective cohort).

ED is a common disorder of male sexual function that affects all age groups and has a profound impact on quality of life. Given the increasing trends in life expectancy across the Western world (i.e., the aging of the general population) and the high prevalence of diabetes and cardiovascular disease, the impact on lifestyle and quality of life imposed by ED in men is projected to be substantial.

– It was estimated that, in 1995, over 152 million men worldwide experienced ED.

– For 2025, the prevalence of ED is predicted to be approximately 322 million worldwide.

The severity, prevalence and incidence of ED increase with age.

The Massachusetts Male Aging Study surveyed 1,709 men aged 40–70 years between 1987 and 1989, using a self-administered questionnaire that asked participants to rate themselves as not having ED, or having minimal ED, moderate ED, or complete ED. There was a total prevalence of erectile dysfunction of 52 percent when participants with minimal (17.2 percent), moderate (25.2 percent) and complete (9.6 percent) dysfunction were combined. Both the prevalence and severity of erectile dysfunction increased proportionally with age. When adjusted for age, patients with lower level of education, heart disease, hypertension, and diabetes had a higher probability of ED.

– In the same study, a sample of 847 men without ED at baseline (1987– 1989) was followed prospectively until 1995–1997.

The crude incidence rate of ED in this population was estimated to be about 26 cases per 1,000 man-years (95% CI: 22.5–29.9).

The annual age-specific incidence rate of ED increased with each decade of age.

For example, the incidence rates (and 95% CIs) for men in two age groups of 50–59 and 60–69 years were

29.8 cases per 1,000 man-years (95% CI: 24.0–37.0)

46.4 cases per 1,000 man-years (95% CI: 36.9–58.4), respectively.

In a Canadian cross-sectional survey of primary care facilities, about 50 percent of 3,921 men aged 40–88 years had ED (IIEF “EF” domain score <21). The presence of cardiovascular diseases or diabetes was associated with an increased risk of having ED after adjustment for age and other confounders.